The post synaptic density (PSD) at excitatory glutamatergic synapses is a complex molecular machine which appears to be a key site of information storage. The PSD is so large-approximately 10 billion Da-that a new method depending on rotary shadowing of immunogold labeled PSDs had to be developed to understand the organization of its numerous molecular components. A lattice-like structure labeling for PSD-95 forms its core, while other structural components-synGAP, certain spectrin isoforms, SHANK, and the kinase CaMKII-occupy various locations at the lattice (but not all components of the PSD faction localize at PSDs). Since activation of CaMKII involves binding calmodulin, a second role for CaMKII (present in large amounts in neurons) is thought to be regulation of calmodulin levels. Recent experiments show that during ischemic stress CaMKII temporarily aggregates into small clusters which maintain the function of buffering calmodulin levels. This clustering would also isolate CaMKII, thereby protecting the neuron from activated CaMKII run rampant. We have now discovered that clustering of CaMKII also occurs at the PSD s in cultured hippocampal neurons during episodes of physiological activity, suggesting new interpretations for its role in information storage.